title: Yersinia enterocolitica inactivates NK cells.
abstract: Natural Killer (NK) cells serve as an important source of proinflammatory cytokines early during infection. Hypothesizing that Yersinia enterocolitica might interact with and inactivate NK cells, we examined NK cell-Y. enterocolitica interactions in vitro and in vivo. Y. enterocolitica adheres to NK cells in an Invasin dependent manner and inhibits NK cell cytotoxicity and IFN-γ production induced by IL-12+IL-18 or IL-12 alone. YopP, an acetyltransferase known to inhibit MAPK and NFκB signaling, suppresses IL-12 and IL-12+IL-18 mediated IFN-γ production in NK cells by inhibiting phosphorylation of Tyk2 and STAT4 in addition to MAPK. YopP inhibits induction of all genes whose expression is induced by IL-12+IL-18 in NK cells. Y. enterocolitica-mediated adherence to and inactivation of NK cells also occurs after infection in vivo. Thus, we present the first report of a bacterial pathogen inactivating NK cells, and report interaction with Tyk2-STAT4 signaling as a novel function of YopP.
authors.affiliation: Ludwig Maximilians University, Max von Pettenkofer Institut, Department of Bacteriology, 80336 Munich, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Koch
authors.forename: Kristina
authors.initials: K
authors.lastname: Dach
authors.forename: Jürgen
authors.initials: J
authors.lastname: Heesemann
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism; D015009:Yersinia Infections / Q000276:immunology*; D015008:Yersinia enterocolitica / Q000276:immunology* / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D037521:Virulence Factors; C109227:YopP protein, Yersinia
keywords: Host pathogen interaction; Infection immunology; Susceptibility to infection